DESC:
FIELD
The present disclosure relates to a process for preparing 4-isobutoxybenzylamine acetate.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
4-Isobutoxybenzylamine acetate is an important intermediate used in the synthesis of pimvanserin, a drug used in the treatment of hallucinations and delusions in psychosis associated with Parkinsons Disease. Conventionally, the condensation reaction of 4-isobutoxybenzaldehyde and hydroxylamine hydrochloride is carried out in a polar protic solvent such as ethanol, to provide 4-isobutoxybenzaldehyde oxime, followed by reduction and treatment with acetic acid to provide 4-isobutoxybenzylamine acetate. However, in the conventional method for the preparation of 4-isobutoxybenzylamine acetate, the yields and purity are poor.
There is, therefore, felt a need for developing a process for preparing 4-isobutoxybenzylamine acetate that mitigates the drawbacks mentioned herein above.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
An object of the present disclosure is to provide a process for the preparation of 4-isobutoxybenzylamine acetate.
Another object of the present disclosure is to provide 4-isobutoxybenzylamine acetate having comparatively high purity and in high yields.
Yet another object of the present disclosure is to provide a simple, cost-effective, environmentally-friendly and an industrially suitable process for the preparation of 4-isobutoxybenzylamine acetate.
Other objects of the present invention will be more apparent to a person skilled in the art from the description provided hereinafter.
SUMMARY
The present disclosure provides a process for preparation of 4-isobutoxybenzylamine acetate. The process comprises alkylating 4-hydroxybenzaldehyde with isobutylbromide in dimethylformamide, in the presence of potassium iodide and potassium carbonate to obtain a first reaction mixture comprising 4-isobutoxybenzaldehyde. 4-isobutoxybenzaldehyde is separated from the first reaction mixture and condensed with hydroxylamine hydrochloride (NH2OH.HCl) to obtain a second reaction mixture comprising 4-isobutoxybenzonitrile. 4-isobutoxybenzonitrile is separated from the second reaction mixture and reduced to obtain a third reaction mixture comprising 4-isobutoxybenzylamine. 4-isobutoxybenzylamine is separated from the third reaction mixture. 4-isobutoxybenzylamine is treated with acetic acid to obtain a product mixture comprising 4-isobutoxybenzylamine acetate. 4-isobutoxybenzylamine acetate is separated from the product mixture.
In accordance with the present disclosure, the step of separating the 4-isobutoxybenzylamine acetate involves cooling the product mixture to a temperature in the range of 15 °C to 25 °C, and then stirring for a time period in the range of 0.5 hour to 1.5 hours, to form a precipitate of 4-isobutoxybenzylamine acetate, which is filtered and washed with toluene to obtain 4-isobutoxybenzylamine acetate.
DETAILED DESCRIPTION
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details, are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
4-isobutoxybenzylamine acetate is an important intermediate in the synthesis of pimvanserin. The present disclosure provides a simple process for preparing 4-isobutoxybenzylamine acetate.
The process of the present disclosure for preparing 4-isobutoxybenzylamine acetate involves the following steps:
1) Preparation of 4-isobutoxybenzaldehyde of formula (IV), from 4-hydroxybenzaldehyde (III) and isobutyl bromide (II);

Step-I: Preparation of 4-isobutoxybenzaldehyde

2) Preparation of 4-isobutoxybenzonitrile of formula (V), from isobutoxybenzaldehyde (IV) and hydroxylamine hydrochloride;

Step-II: Preparation of 4-isobutoxybenzonitrile (V)
and

3) Preparation of 4-isobutoxybenzylamine acetate of formula (I), from 4-isobutoxybenzonitrile (V).

Step-III: Preparation of 4-isobutoxybenzylamine acetate
In the first step, i.e., the alkylation of 4-hydroxybenzaldehyde (III) with isobutylbromide (II) is carried out in the presence of potassium iodide and potassium carbonate (K2CO3), in dimethylformamide (DMF).
The alkylation of 4-hydroxybenzaldehyde (III) with isobutyl bromide (II) is carried out in a suitable reactor under stirring in an inert atmosphere. N, N-dimethylformamide (DMF) is introduced in the reactor followed by the addition of 4-hydroxybenzaldehyde at a temperature in the range of 25 to 30 oC to obtain a mixture. Thereafter, potassium carbonate and potassium iodide are added to the mixture in the reactor. The resultant mixture is heated at a temperature in the range of 75 to 85 oC, and isobutyl bromide is added slowly to the heated mixture over a predetermined time period, to obtain a first reaction mixture.
In accordance with the embodiments of the present disclosure, the molar ratio of potassium carbonate to 4-hydroxybenzaldehyde (III) is in the range of 1:1 to 3:1. In an embodiment of the present disclosure, the molar ratio of potassium carbonate to 4-hydroxybenzaldehyde (III) is 2:1.
In accordance with the embodiments of the present disclosure, the molar ratio of potassium iodide to 4-hydroxybenzaldehyde (III) is in range of 1:9 to 1:11. In an embodiment of the present disclosure, the molar ratio of potassium iodide to 4-hydroxybenzaldehyde (III) is 1:10.
In accordance with the embodiments of the present disclosure, isobutyl bromide is added over a predetermined time period in the range of 1 to 5 hours. In an embodiment of the present disclosure, isobutyl bromide is added over a time period of 4 hours.
The first reaction mixture is stirred in an inert atmosphere for a time period in the range of 3 to 5 hours at a temperature in the range of 75 to 85 oC. The first reaction mixture is monitored for the utilization of (III) using Gas Chromatography (GC) or other suitable spectroscopic techniques.
After completion of the reaction, the first reaction mixture is cooled to 28 oC and filtered to remove solids and obtain a first filtrate. Water and dichloromethane are added to the first filtrate at 28 oC, to obtain a first biphasic mixture, which is stirred for 30 minutes. The first biphasic mixture is allowed to settle and separate into a first organic layer and a first aqueous layer. The first organic layer is separated from the first aqueous layer, and then the first aqueous layer is acquired, washed with dichloromethane to obtain a second organic layer and a second aqueous layer. The second organic layer is separated from the second aqueous layer, and the separated first and second organic layers are combined, and the combined organic layer is heated to distill off dichloromethane, and then 4-isobutoxybenzaldehyde (IV) is distilled under high vaccum at 150-160 oC.
In one embodiment of the present disclosure, the yield of 4-isobutoxybenzaldehyde (IV), is found to be 77 % and the purity of 4-isobutoxybenzaldehyde (IV), is found to be 99%.
In the second step, intermediate compound of formula (IV) obtained in the first step is subjected to a condensation reaction with hydroxylamine hydrochloride (NH2OH.HCl).
The condensation reaction of 4-isobutoxybenzaldehyde (IV) with hydroxylamine hydrochloride (NH2OH.HCl) is carried out under an inert atmosphere in a suitable reactor under stirring. Hydroxylamine hydrochloride (NH2OH.HCl) is added in portions to a mixture of 4-isobutoxybenzaldehyde (IV) in a polar aprotic solvent in a reactor, to obtain a second reaction mixture.
The polar aprotic solvent is selected from the group consisting of Acetonitrile (MeCN), Tetrahydrofuran (THF), Ethyl acetate (EtOAc), Dimethylformamide (DMF), Acetone (Me2CO), and Dimethylsulfoxide (DMSO). In one embodiment of the present disclosure, the polar aprotic solvent is acetonitrile (MeCN).
The molar ratio of 4-isobutoxybenzaldehyde (IV) to hydroxyalamine hydrochloride (NH2OH.HCl) is in the range of 1:1 to 1:3. In an embodiment of the present disclosure, the molar ratio of 4-isobutoxybenzaldehyde (IV) to hydroxyalamine hydrochloride (NH2OH.HCl) is 1: 1.28.
The molar ratio of hydroxyalamine hydrochloride (NH2OH.HCl) to the polar aprotic solvent is in the range of 1:9 to 1:18. In an embodiment of the present disclosure, the molar ratio of hydroxyalamine hydrochloride (NH2OH.HCl) to the polar aprotic solvent is 1:13.3.
The condensation reaction of 4-isobutoxybenzaldehyde (IV) with hydroxylamine hydrochloride (NH2OH.HCl) is carried out at a temperature in the range of 75 ?C to 85 ?C. In an embodiment of the present disclosure, the condensation reaction of 4-isobutoxybenzaldehyde (IV) with hydroxylamine hydrochloride (NH2OH.HCl) is carried out at 80 ?C
The condensation reaction of 4-isobutoxybenzaldehyde (IV) with hydroxylamine hydrochloride (NH2OH.HCl) is carried out for a time period in the range of 4 to 8 hours. In an embodiment of the present disclosure, the condensation reaction of 4-isobutoxybenzaldehyde (IV) with hydroxylamine hydrochloride (NH2OH.HCl) is carried out for 5 hours.
In a preferred embodiment of the present disclosure, the condensation reaction of 4-isobutoxybenzaldehyde (IV) and hydroxyalamine hydrochloride is monitored for the utilization of (IV) using Gas Chromatography (GC) or other suitable spectroscopic techniques.
The mixture containing 4-isobutoxybenzaldehyde to hydroxyalamine hydrochloride (NH2OH.HCl) in the polar aprotic solvent is stirred under an inert atmosphere.
After completion of reaction, the second reaction mixture is cooled to 50 oC followed by addition of water to dilute the second reaction mixture at 50 oC. The diluted polar aprotic solvent is distilled under reduced pressure and the resultant aqueous mass is cooled to 25 oC to 30 oC and dichloromethane is added to obtain a second biphasic mixture, which is stirred for 30 minutes. The second biphasic mixture is allowed to settle and separate into a dichloromethane layer and a water layer. The dichloromethane layer is heated to distill off dichloromethane, to obtain a residue. The residue is dried under reduced pressure at 50 °C to obtain 4-isobutoxybenzonitrile in the form of a light brown oil, which is directly used for the next step.
In an embodiment of the present disclosure, the yield of 4-isobutoxybenzonitrile (V) is found to be 94 %, and the purity of 4-isobutoxybenzonitrile (V) is found to be 98%.
The present disclosure uses a polar aprotic solvent such as acetonitrile for carrying out the condensation reaction of 4-isobutoxybenzaldehyde (IV) with hydroxylamine to obtain 4-isobutoxybenzonitrile (IV) as product.
In the present disclosure, isolation of 4-isobutoxybenzonitrile (V) involves simple procedures such as extraction with dichloromethane, followed by evaporation of dichloromethane.
In the third step, 4-isobutoxybenzonitrile (IV) is reduced by using hydrogen gas in the presence of methanolic ammonia and catalytic amount of Raney-Nickel.
The reduction of 4-isobutoxybenzontrile (V) is carried out in a suitable reactor. 4-Isobutoxybenzontrile (V) is added to a mixture of Raney Nickel and methanolic ammonia, under stirring in a reactor, and then hydrogen gas is passed in the reactor to obtain a third reaction mixture.
In accordance with the embodiments of the present disclosure, 4-isobutoxybenzonitrile is reduced by using hydrogen gas, at a pressure in the range from 100 psi to 130 psi, at a temperature in the range of 50 °C to 70 °C. In an embodiment of the present disclosure, 4-isobutoxybenzonitrile is reduced by using hydrogen gas at a pressure of 115 psi and at a temperature of 60 °C.
The concentration of ammonia in the methanolic ammonia used in the present disclosure is 10% ammonia in methanol.
In a preferred embodiment of the present disclosure, the step of reduction is monitored for the utilization of 4-isobutoxybenzonitrile (V), using Gas Chromatography (GC) or other suitable spectroscopic techniques.
On completion of the reduction reaction, the third reaction mixture comprising the catalyst Raney Nickel is filtered and the filtrate is heated to distill methanol under under reduced pressure to obtain a residue comprising a thick liquid.
4-Isobutoxybenzylamine is treated with acetic acid, by slowly adding acetic acid to a mixture of the residue in toluene to obtain a product mixture comprising 4-isobutoxybenzylamine acetate.
Toluene is added to the residue of thick liquid at 28 oC, followed by dropwise addition of acetic acid over 1 hour at 33 oC and stirring for 1 hour to obtain a product mixture. The reaction mass is cooled to 18 oC, stirred for 1 hour and then filtered to obtain solids, which are washed with toluene, to obtain 4-isobutoxybenzylamine acetate (I) with a yield of 62 % and having a purity of 98%.
The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be tested to scale up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
EXPERIMENTAL DETAILS
Example 1: Preparation of 4-isobutoxybenzylamine acetate (I) from 4-Hydroxybenzaldehyde (III)
Step-1: Preparation of 4-isobutoxybenzaldehyde:
4-Hydroxybenzaldehyde (1.0 kg) was dissolved in N, N-dimethylformamide (2.75 L), under stirring at 30 oC, in a reactor, followed by addition of potassium carbonate (2.29 kg) and potassium iodide (0.14 kg), further followed by heating to 80 oC, and then adding isobutyl bromide (2.25 kg) over 4 hours to obtain a first reaction mixture, which was maintained at 80 °C for 5 hrs, to obtain a first reaction mixture comprising 4-isobutoxybenzaldehyde. The first reaction mixture was monitored by GC. After 5 hours, the first reaction mixture showed absence of starting material by GC. After completion of the reaction, the first reaction mixture was cooled to 28 oC, filtered to remove solids and obtain a first filtrate comprising 4-isobutoxybenzaldehyde. Water (7.5 L) and Dichloromethane (3 L) were added to the first filtrate to obtain a first biphasic mixture, which was stirred for 30 minutes and then allowed to settle to separate into a first organic layer and a first aqueous layer. The first organic layer was separated from the first aqueous layer and the first organic layer was heated to distill dichloromethane at 45oC, first under atmospheric pressure and then under reduced pressure to obtain a thick liquid, which was distilled at 155 oC, under reduced pressure to collect 4-isobutoxybenzaldehyde (1 kg, Yield = 77%, Purity (GC) = 99%) as a brown liquid that was taken to the next reaction.
Step-2: Preparation of 4-isobutoxybenzonitrile:
Hydroxylamine hydrochloride (150.0 g) was added in portions to a mixture of 4-isobutoxybenzaldehyde (300 g) and acetonitrile (1.5 L) at 28 oC, in a reactor, to obtain a second reaction mixture. The second reaction mixture was heated at 80 oC for 5 hours to obtain a second reaction mixture comprising 4-isobutoxybenzonitrile. The second reaction mixture was monitored by GC. After 5 hours, the second reaction mixture showed absence of starting material by GC. After completion of the reaction, the second reaction mixture was cooled to 50 oC. Water (300 ml) was added to the cooled second reaction mixture and the diluted second reaction mixture was heated at 50 oC to 55 oC to distill acetonitrile under reduced pressure to obtain an aqueous mixture. The aqueous mixture was cooled to 28 oC and dichloromethane (1.2 L) was added to the cooled aqueous mixture to obtain a second biphasic mixture that was stirred for 30 minutes. The second biphasic mixture was allowed to settle and separate into a dichloromethane layer and a water layer. The dichloromethane layer was separated from the water layer and the separated dichloromethane layer was heated to distill dichloromethane to obtain a residue that was dried under reduced pressure at 50 ?C to obtain 4-isobutoxybenzonitrile (280 g, Yield = 94%, Purity (GC) = 98%) in the form of a light brown oil, which was used as such in the next step. 1H and 13C NMR data of 4-isobutoxy benzonitrile is presented below.
1H NMR: - d (CDCl3, 300 MHz), 1.02 (d, 6H), 2.1 (m, 1H), 3.8 (d, 2H), 6.95 (d, 2H), 7.6 (d, 2H).
13C NMR: - d (CDCl3, 75 MHz), 20.5 (2*CH3), 29.5, (CH), 75.0 (CH2), 104.0 (Ar-C), 117.0 (2*Ar-CH), 120.0 (Ar-C), 135.0 (2*Ar-CH), 163.0 (CN).
Step-3: Preparation of 4-isobutoxybenzylamine acetate:
4-Isobutoxybenzonitrile (280 g) in a third reaction mixture comprising methanolic ammonia (10% ammonia in methanol, 2L) was reduced with hydrogen (H2 gas), at a pressure of 115 psi, at 60 oC, in the presence of Raney/Ni catalyst (28 g). The third reaction mixture was monitored by GC. After 5 hours, the third reaction mixture showed absence of starting material by GC. After completion of the reaction, the third reaction mixture was filtered to remove the catalyst and the second filtrate was heated at 55 oC to distill methanol under reduced pressure to obtain a thick liquid. Toluene (1.0 L) was added to the thick liquid at 28 oC, followed by dropwise addition of acetic acid (120 g) over 1 hour at 33 oC, and stirring for 1 hour to obtain a product mixture. The product mixture was cooled to 18 oC, stirred for 1 hour, and filtered to collect solids, which were washed with toluene (100 ml) to obtain 4-isobutoxybenzylamine acetate (245g, Yield = 62%, Purity = 99%).
TECHNICAL ADVANCES AND ECONOMICAL SIGNIFICANCE
The process of the present disclosure described herein above has several technical advantages including but not limited to the realization of a process for the synthesis of 4-isobutoxybenzylamine acetate, that is simple; and provides high yield and high purity.
The disclosure has been described with reference to the accompanying embodiments which do not limit the scope and ambit of the disclosure. The description provided is purely by way of example and illustration.
The embodiments herein and the various features and advantageous details thereof have been explained with reference to the non-limiting embodiments in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The foregoing description of the specific embodiments so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.
,CLAIMS:WE CLAIM:
1. A process for preparation of 4-isobutoxybenzylamine acetate, comprising the following steps:
i. alkylating 4-hydroxybenzaldehyde with isobutylbromide to obtain a first reaction mixture comprising 4-isobutoxybenzaldehyde;
ii. separating 4-isobutoxybenzaldehyde from the first reaction mixture;
iii. condensing 4-isobutoxybenzaldehyde with hydroxylamine hydrochloride (NH2OH.HCl) to obtain a second reaction mixture comprising 4-isobutoxybenzonitrile;
iv. separating 4-isobutoxybenzonitrile from the second reaction mixture;
v. reducing 4-isobutoxybenzonitrile to obtain a third reaction mixture comprising 4-isobutoxybenzylamine;
vi. separating 4-isobutoxybenzylamine from the third reaction mixture;
vii. treating 4-isobutoxybenzylamine with acetic acid to obtain a product mixture comprising 4-isobutoxybenzylamine acetate; and
viii. separating 4-isobutoxybenzylamine acetate from the product mixture.
2. The process as claimed in claim 1, wherein the alkylation is carried out in dimethylformamide, in the presence of potassium iodide and potassium carbonate.
3. The process as claimed in claim 1, wherein the step of separating 4-isobutoxybenzaldehyde from the first reaction mixture involves the following substeps:
a. cooling and filtering the first reaction mixture comprising 4-isobutoxybenzaldehyde to remove solids and collect a first filtrate comprising 4-isobutoxybenzaldehyde; and
b. extracting 4-isobutoxybenzaldehyde in the first filtrate using dichloromethane and distilling dicloromethane to obtain 4-isobutoxybenzaldehyde.
4. The process as claimed in claim 1, wherein in step (iii), the molar ratio of 4-isobutoxybenzaldehyde to hydroxylamine hydrochloride (NH2OH.HCl) is in the range of 1:1 to 1:3.
5. The process as claimed in claim 1, wherein the condensation is carried out in a polar aprotic solvent selected from the group of consisting of acetonitrile (MeCN), tetrahydrofuran (THF), Ethyl acetate (EtOAc), Dimethylformamide (DMF), Acetone (Me2CO), and Dimethylsulfoxide (DMSO).
6. The process as claimed in claim 5, wherein in step (iii), the molar ratio of hydroxylamine hydrochloride (NH2OH.HCl) to the polar aprotic solvent is in the range of 1:20 to 1:35.
7. The process as claimed in claim 1, wherein the condensation in step (iii), is carried out at a temperature in the range of 75 °C to 85 °C, for a time period in the range of 4 hours to 8 hours.
8. The process as claimed in claim 1, wherein the step of separating 4-isobutoxybenzonitrile involves the following substeps:
i. cooling the second reaction mixture comprising 4-isobutoxybenzonitrile, and diluting with water to obtain a diluted mixture;
ii. heating the diluted mixture to distill the polar aprotic solvent to obtain an aqueous mixture comprising 4-isobutoxybenzonitrile; and
iii. extracting 4-isobutoxybenzonitrile in the aqueous mixture using dicloromethane, and distilling dichloromethane to obtain 4-isobutoxybenzonitrile.
9. The process as claimed in claim 1, wherein in step (v), the reduction of 4-isobutoxybenzonitrile is carried out using hydrogen gas, in methanolic ammonia and in the presence of of Raney-Nickel, at a temperature in the range of 50 °C to 70 °C and at a pressure in the range of 100 psi to 130 psi.
10. The process as claimed in claim 9, wherein the methanolic ammonia is 10 wt% ammonia in methanol.
11. The process as claimed in claim 9, wherein the weight ratio of 4-isobutoxybenzonitrile to methanolic ammonia is in the range of 1:6 to 1:8.
12. The process as claimed in claim 9, wherein the weight ratio of raney-nickel to 4-isobutoxybenzonitrile is in the range of 12:1 to 8:1.
13. The process as claimed in claim 1, wherein the step of separating 4-isobutoxybenzylamine involves the following substeps:
a. filtering the third reaction mixture comprising 4-isobutoxybenzylamine to remove Raney-Nickel and obtain a filtrate comprising 4-isobutoxybenzylamine; and
b. heating the filtrate to distill methanol and obtain a residue comprising 4-isobutoxybenzylamine.
14. The process as claimed in claim 1, wherein 4-isobutoxybenzylamine is treated with acetic acid by dissolving the residue comprising 4-isobutoxybenzylamine in toluene to form a solution and slowly adding acetic acid to the solution, at a temperature in the range of 25 °C to 40 °C.
15. The process as claimed in claim 1, wherein the step of separating 4-isobutoxybenzylamine acetate involves cooling the product mixture to a temperature in the range of 15 °C to 25 °C, and then stirring for a time period in the range of 0.5 hour to 1.5 hours, to form a precipitate of 4-isobutoxybenzylamine acetate, which is filtered and washed with toluene to obtain 4-isobutoxybenzylamine acetate.